paediatrics Brussels 17

Ramaswamy et al

A

B

1.00

1.00

0.75

0.75

0.50

0.50

0.25 OS (probability)

0.25 PFS (probability)

Age < 10 years Age > 10 years

Age < 10 years Age > 10 years

P = .21

P = .53

0 1 2 3 4 5 6 7 8 9 10 Time Since Diagnosis (years)

0 1 2 3 4 5 6 7 8 9 10 Time Since Diagnosis (years)

Age < 10 Age > 10 No. at risk

Age < 10 Age > 10 No. at risk

624 545 473 388 327 277 224 184 143 116 93 54 51 42 38 33 29 28 24 21 16 10

623 479 363 283 232 203 162 133 103 83 71 54 48 36 30 25 23 23 20 17 13 7

C

D

1.00

1.00

0.75

0.75

0.50

0.50

0.25

0.25 OS (probability)

PFS (probability)

Age < 18 years Age > 18 years

Age < 18 years Age > 18 years

P = .73

P = .26

0 1 2 3 4 5 6 7 8 9 10 Time Since Diagnosis (years)

0 1 2 3 4 5 6 7 8 9 10 Time Since Diagnosis (years)

Age < 18 Age > 18 No. at risk

Age < 18 Age > 18 No. at risk

48 45 43 38 29 24 18 11 10 7 6 93 85 78 69 60 55 49 43 34 25 18

47 40 35 31 23 20 15 10 9 6 5 94 84 75 65 56 51 45 38 30 22 17

Fig 1. Survival of EPN_PFA and EPN_PFB strati fi ed by age. (A) Progression-free survival (PFS) and (B) overall survival (OS) of EPN_PFA strati fi ed by age greater than or less than 10 years. (C) PFS and (D) OS of EPN_PFB strati fi ed by age greater than or less than 18 years. P values determined using log-rank test.

previously observed therapeutic value for surgical cytoreduction was confounded by the poor natural history of EPN_PFA tumors, which are dif fi cult to resect, compared with the benign natural history of EPN_PFB tumors, which are less dif fi cult to resect. To determine the relationship between subgroup and extent of resection after accounting for molecular subgroup, we compared PFS and OS in each subgroup individually strati fi ed by extent of resection. When comparing subtotal resection (STR) versus gross total resection (GTR) in EPN_PFA, STR was highly predictive of a dismal PFS and OS ( Fig 2 and Appendix Table A6 , online only). In a multivariable Cox proportional hazards model that included adjuvant chemotherapy and radiation, survival remained dismal for STR EPN_PFA (Appendix Tables A7 and A8 , online only). Although we observed some variability in the effect of extent of

resection across the four cohorts, we did not observe a statistically signi fi cant difference in or heterogeneity of the effect of extent of resection in EPN_PFA across cohorts (interaction P = .80 for PFS, P = .53 for OS). Male sex was a signi fi cant independent predictor of poor outcome across all four cohorts in GTR in a multivariable analysis restricted to EPN_PFA, although STR is a high-risk group in both male and female patients (Appendix Fig A5 , online only, and Appendix Table A7 ). Within EPN_PFA, female patients with a GTR had a 5-year PFS of 0.652 (95% CI, 0.581 to 0.732), whereas male patients with a GTR had a 5-year PFS of 0.455 (95% CI, 0.393 to 0.527). The value of fi rst-line (adjuvant post-surgical) radiotherapy could only be compared with no radiation in the GENE, CERN, and Burdenko cohorts, because all patients in the prospective

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